Florasulam is a three azole and pyrimidine sulfonamide herbicide, mainly used for weeds prevention and control in winter wheat fields. The main purpose of this experiment was to study the effects of different doses of Florasulam on soil residues and on the enzymatic activity of wheat cultivated in drylands, and to provide the theoretical basis for a scientific use of florasulam. Five doses (0, 15, 30, 45, and 60 mL/667 m2) of Florasulam were applied in order to detect differences in soil residue content and enzymatic activities. Soil residues and enzymatic activities (catalase, phosphatase, urease, dehydrogenase) were measured and analyzed after the 5 different doses of Florasulam were processed. The residual amount of Florasulam in the soils decreased gradually with the growth phase of wheat, and was lower than that of 0.01 mg/kg. The residual amount of Florasulam in different soil layers gradually decreased with the increase of soil thickness. The enzymatic activity of soils treated with Florasulam was basically T3 > T2 > T1 > CK > T4, where T3 was the highest, whereas T4 could inhibit the enzymatic activity. Under these experimental conditions, in order to decrease soil pollution and lower Florasulam residues, it is recommended to apply Florasulam at a concentration range of 30 to 45 mL/667 m2.